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RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function

RBFOX3 mutations are linked to epilepsy and cognitive impairments, but the underlying pathophysiology of these disorders is poorly understood. Here we report replication of human symptoms in a mouse model with disrupted Rbfox3. Rbfox3 knockout mice displayed increased seizure susceptibility and decr...

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Autores principales: Wang, Han-Ying, Hsieh, Pei-Fen, Huang, De-Fong, Chin, Pey-Shyuan, Chou, Chih-Hsuan, Tung, Chun-Che, Chen, Shin-Yuan, Lee, Li-Jen, Gau, Susan Shur-Fen, Huang, Hsien-Sung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664964/
https://www.ncbi.nlm.nih.gov/pubmed/26619789
http://dx.doi.org/10.1038/srep17383
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author Wang, Han-Ying
Hsieh, Pei-Fen
Huang, De-Fong
Chin, Pey-Shyuan
Chou, Chih-Hsuan
Tung, Chun-Che
Chen, Shin-Yuan
Lee, Li-Jen
Gau, Susan Shur-Fen
Huang, Hsien-Sung
author_facet Wang, Han-Ying
Hsieh, Pei-Fen
Huang, De-Fong
Chin, Pey-Shyuan
Chou, Chih-Hsuan
Tung, Chun-Che
Chen, Shin-Yuan
Lee, Li-Jen
Gau, Susan Shur-Fen
Huang, Hsien-Sung
author_sort Wang, Han-Ying
collection PubMed
description RBFOX3 mutations are linked to epilepsy and cognitive impairments, but the underlying pathophysiology of these disorders is poorly understood. Here we report replication of human symptoms in a mouse model with disrupted Rbfox3. Rbfox3 knockout mice displayed increased seizure susceptibility and decreased anxiety-related behaviors. Focusing on hippocampal phenotypes, we found Rbfox3 knockout mice showed increased expression of plasticity genes Egr4 and Arc, and the synaptic transmission and plasticity were defective in the mutant perforant pathway. The mutant dentate granules cells exhibited an increased frequency, but normal amplitude, of excitatory synaptic events, and this change was associated with an increase in the neurotransmitter release probability and dendritic spine density. Together, our results demonstrate anatomical and functional abnormality in Rbfox3 knockout mice, and may provide mechanistic insights for RBFOX3-related human brain disorders.
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spelling pubmed-46649642015-12-03 RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function Wang, Han-Ying Hsieh, Pei-Fen Huang, De-Fong Chin, Pey-Shyuan Chou, Chih-Hsuan Tung, Chun-Che Chen, Shin-Yuan Lee, Li-Jen Gau, Susan Shur-Fen Huang, Hsien-Sung Sci Rep Article RBFOX3 mutations are linked to epilepsy and cognitive impairments, but the underlying pathophysiology of these disorders is poorly understood. Here we report replication of human symptoms in a mouse model with disrupted Rbfox3. Rbfox3 knockout mice displayed increased seizure susceptibility and decreased anxiety-related behaviors. Focusing on hippocampal phenotypes, we found Rbfox3 knockout mice showed increased expression of plasticity genes Egr4 and Arc, and the synaptic transmission and plasticity were defective in the mutant perforant pathway. The mutant dentate granules cells exhibited an increased frequency, but normal amplitude, of excitatory synaptic events, and this change was associated with an increase in the neurotransmitter release probability and dendritic spine density. Together, our results demonstrate anatomical and functional abnormality in Rbfox3 knockout mice, and may provide mechanistic insights for RBFOX3-related human brain disorders. Nature Publishing Group 2015-12-01 /pmc/articles/PMC4664964/ /pubmed/26619789 http://dx.doi.org/10.1038/srep17383 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Wang, Han-Ying
Hsieh, Pei-Fen
Huang, De-Fong
Chin, Pey-Shyuan
Chou, Chih-Hsuan
Tung, Chun-Che
Chen, Shin-Yuan
Lee, Li-Jen
Gau, Susan Shur-Fen
Huang, Hsien-Sung
RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function
title RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function
title_full RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function
title_fullStr RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function
title_full_unstemmed RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function
title_short RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function
title_sort rbfox3/neun is required for hippocampal circuit balance and function
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664964/
https://www.ncbi.nlm.nih.gov/pubmed/26619789
http://dx.doi.org/10.1038/srep17383
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